A continuation of our work on the metabolic mechanisms underlying the periodicity and spontaneity of interictal seizure discharge is proposed. Using cat as an experimental animal, acute epileptogenic foci will be created on the exposed dorsal hippocampus via topical application of sodium penicillin. The exposed hippocampal field will then be covered by a pool of warm artificial cerebrospinal fluid (CSF) which can later be exchanged for CSF of altered composition. The effects of procedures or agents significant to Na-K coupled ATP-ase activity (such as anoxia, hyperventilation, temperature, ouabain, Li, K, Ca or Mg in CSF) on magnitude and form of the spontaneous interictal discharge, as well as upon the mean duration and distribution of the interspike intervals, will be examined. These data will be compared with the effects of the same procedures or agents on excitability of naive hippocampus under artificial CSF. Hippocampal reactivity before and after the above manipulations will be measured in terms of the amplitude of the negative field component in response to antidromic fornix (and/or commissural) stimulation. Simultaneous study of single unit discharge patterns will contribute to the interpretation of these data, as rill laminar analysis of the fields. In parallel experiments, the hippocampal penicillin focus will be examined in rats as a potential method with which to quantify effects of and to dicriminate between possible methods of action of anti-epileptic drugs. Validation of this technique will include demonstration of agreement of the interspike interval data with the known dose-response data of such drugs. Where necessary, seizure threshold data will be obtained and compared with the interictal spike modulation rate data. The general objectives of this work are to characterize the role of Na-K coupled ATP-ase in the expression of seizure and to develop a new method for the evaluation of anti-epileptic drugs.